The Prostate 75:1^7 (2015)
Salvage Focal Prostate Cryoablation for Locally Recurrent Prostate Cancer After Radiotherapy: Initial Results From the Cryo On-Line Data Registry Yong-Hong Li,1,2 Ahmed Elshafei,1 Gautum Agarwal,3 Herbert Ruckle,4 Julio Pow-Sang,3 and J. Stephen Jones1* 1
Glickman Urologicaland Kidney Institute,Cleveland Clinic,Cleveland,Ohio Department of Urology,Cancer Center, SunYat-Sen University,Guangzhou, People’s Republic of China 3 Department of Genitourinary Oncology, Moff|tt Cancer Center & Research Institute,Tampa, Florida 4 Department of Urology, Loma Linda University, Loma Linda,California
2
BACKGROUND. Several investigators have tried to apply salvage focal prostate cryoablation to small numbers of patients with biopsy-proven unilateral recurrent prostate cancer (PCa) after radiotherapy with the aim of decreasing complications of salvage cryoablation. We report contemporary outcomes of salvage focal cryoablation for locally recurrent PCa after radiotherapy within the Cryo On-Line Data (COLD) Registry. METHODS. We queried the COLD Registry to identify patients diagnosed as locally recurrent PCa after radiotherapy and treated with salvage focal cryoablation. Patients with hormone ablation after cryotherapy were excluded. The biochemical disease-free survival and morbidities were analyzed. Biochemical failure was defined using the Phoenix definition. RESULTS. From 2002 to 2012, 91 patients with biopsy-proven radio-recurrent PCa underwent salvage focal cryoablation with curative intent. The biochemical disease-free survival rates were 95.3%, 72.4%, and 46.5% at 1, 3, and 5 years, respectively. Positive biopsies after salvage focal cryoablation were observed in four of 14 patients who underwent biopsy (28.6%). Rectourethral fistula was observed in three cases (3.3%). Urinary retention was observed in six cases (6.6%). Incontinence (requiring pad use) was reported in five cases (5.5%). Intercourse was reported in 10 of 20 patients (50%) who reported potency before salvage focal cryoablation. CONCLUSIONS. The outcomes from this observational study indicate that salvage focal cryoablation can be an effective treatment with encouraging potency preservation for patients with locally recurrent PCa after radiotherapy. However, other morbidity including rectourethral fistula and incontinence are not clearly lower than for patients treated with salvage whole gland cryoablation. Studies with longer follow-up, more patients, and direct comparison to salvage whole gland cryoablation are needed before recommending salvage focal cryoablation as a standard treatment option for these patients. Prostate 75: 1–7, 2015. # 2014 Wiley Periodicals, Inc.
KEY WORDS:
cryoablation; focal therapy; prostate cancer; radiotherapy; salvage
Herbert Ruckle (Olympus). Julio Powsang (Watermark Research). J. Stephen Jones (Predictive Biosciences, Photocare, Healthtronics, Cook). Conflict of interest: Nothing to declare (Yong-Hong Li, Ahmed Elshafei, Gautum Agarwal)
Correspondence to: J. Stephen Jones, MD, Vice President Regional Medical Operations Cleveland Clinic Regional Hospitals & Family Health Centers Professor & Horvitz/Miller Distinguished Chair 9500 Euclid Avenue, Q10-1, OH 44195. E-mail: [email protected] Received 6 July 2014; Accepted 23 July 2014 DOI 10.1002/pros.22881 Published online 4 October 2014 in Wiley Online Library (wileyonlinelibrary.com).
ß 2014 Wiley Periodicals, Inc.
2
Li et al.
INTRODUCTION Approximately 25% patients with prostate cancer (PCa) undergo radiotherapy as a primary treatment option according to SEER (Surveillance, Epidemiology and End Results) data [1]. Biochemical failure after radiotherapy for localized PCa can occur in approximately 10–60% [2–4]. The most common salvage treatment for these patients is androgen-deprivation therapy [3]. However, this is not a curative treatment. Furthermore, it can have an impact on quality of life and increase the risk of cardiovascular mortality and skeletal fracture [5]. Many patients with biopsy-proven locally recurrent PCa may be suitable for local salvage therapy with curative intent. Local salvage treatment options include radical prostatectomy (RP), cryoablation, high-intensity focused ultrasonography, and brachytherapy. Since salvage RP is limited in clinical practice due to much higher morbidity than primary RP [6], salvage whole gland cryoablation has emerged as an option with acceptable long-term oncological outcomes and lower side effects. However, significant side effects are possible, including urinary retention (3.0–8.5%), incontinence (4.4–13.0%), rectourethral fistula (0–3.3%), and erectile dysfunction (61.5–100%) [7,8,9]. In order to decrease complications of salvage cryoablation, several investigators have tried to apply salvage focal cryoablation to small numbers of patients with biopsy-proven unilateral recurrent PCa after radiotherapy. Salvage focal cryoablation of the prostate for locally recurrent PCa after radiotherapy failure was first reported by Eisenberg and Shinohara in 2008 [10]. Several recent publications also showed encouraging outcomes of salvage focal cryoablation for locally recurrent PCa after radiotherapy failure. However, all these studies had small patients’ numbers (the biggest number is 44 patients) [9,11,12]. In this study, we report the outcomes of salvage focal cryoablation at a large number of academic and community centers that have participated in the COLD Registry. To our knowledge, this is the largest data set assembled for salvage focal cryoablation for the treatment of localized PCa recurrence after radiotherapy.
MATERIALS AND METHODS The COLD Registry was developed in an effort to provide a platform for academic and community urologists to gather cumulative data to advance the awareness and science of prostate cryoablation through evidence-based medical outcomes. Currently, The Prostate
over 7,000 patient records from 44 active sites are included in the registry. Although industry sponsored (HealthTronics; Austin, TX), all registry data collection, statistical analysis, and reporting was performed by an independent research company (Watermark Research Partners; Indianapolis, IN). The COLD Registry is supervised by a scientific board of urologists, and an independent audit of the scientific data is conducted yearly at randomly chosen centers in order to ensure the accuracy of data. All participating sites that were required to do so had approval from their institutional review board (IRB) before submission of any data to the registry database. A global IRB protocol has been in place since 2006 [13,14]. Patient data were entered into the COLD Registry classified as “primary” or “salvage” cryoablation and were further divided into “whole-gland” and “partial-gland” cryoablation. The use of neoadjuvant hormone ablation before cryoablation and adjuvant hormone ablation after cryoablation was noted. On November 5, 2013, we queried the COLD Registry to identify men who had undergone salvage partial gland prostate cryoablation for locally recurrent PCa after radiotherapy between 1999 and 2012. A total of 102 patients have undergone salvage focal cryotherapy within the COLD Registry. Eleven patients that received adjuvant hormone ablation were excluded from the study because of the likelihood that prostate specific antigen (PSA) values were misleadingly reduced by androgen deprivation. Ninety-one patients served as our study population. Any patient that had any length of androgen deprivation prior to treatment was defined as having neoadjuvant hormonal ablation, even if the purpose of this precryoablation treatment was unknown. Incontinence was defined as any pad use 12 months after salvage focal cryoablation. Potency was defined by the ability to have intercourse 12 months after salvage focal cryoablation. Post salvage focal cryoablation prostate biopsy was performed at physician discretion. Biochemical failure was defined using the Phoenix definition (nadir þ 2 ng/ml), which is the most commonly reported criterion, since no universally accepted definition of success has been identified in this setting [15]. Data were summarized using descriptive statistics. Continuous variables were compared with the Mann– Whitney U-test and categorical variables were compared with the Chi-squared test or Fisher’s exact test, as appropriate. The Kaplan–Meier method was used in the assessment of biochemical disease-free survival (bDFS) for the entire study population and for our subgroup analysis of bDFS stratified by neoadjuvant hormone ablation status. All statistics were two-sided,
Salvage Focal Prostate Cryoablation
3
and a P-value of
Salvage Focal Prostate Cryoablation for Locally Recurrent Prostate Cancer After Radiotherapy: Initial Results From the Cryo On-Line Data Registry Yong-Hong Li,1,2 Ahmed Elshafei,1 Gautum Agarwal,3 Herbert Ruckle,4 Julio Pow-Sang,3 and J. Stephen Jones1* 1
Glickman Urologicaland Kidney Institute,Cleveland Clinic,Cleveland,Ohio Department of Urology,Cancer Center, SunYat-Sen University,Guangzhou, People’s Republic of China 3 Department of Genitourinary Oncology, Moff|tt Cancer Center & Research Institute,Tampa, Florida 4 Department of Urology, Loma Linda University, Loma Linda,California
2
BACKGROUND. Several investigators have tried to apply salvage focal prostate cryoablation to small numbers of patients with biopsy-proven unilateral recurrent prostate cancer (PCa) after radiotherapy with the aim of decreasing complications of salvage cryoablation. We report contemporary outcomes of salvage focal cryoablation for locally recurrent PCa after radiotherapy within the Cryo On-Line Data (COLD) Registry. METHODS. We queried the COLD Registry to identify patients diagnosed as locally recurrent PCa after radiotherapy and treated with salvage focal cryoablation. Patients with hormone ablation after cryotherapy were excluded. The biochemical disease-free survival and morbidities were analyzed. Biochemical failure was defined using the Phoenix definition. RESULTS. From 2002 to 2012, 91 patients with biopsy-proven radio-recurrent PCa underwent salvage focal cryoablation with curative intent. The biochemical disease-free survival rates were 95.3%, 72.4%, and 46.5% at 1, 3, and 5 years, respectively. Positive biopsies after salvage focal cryoablation were observed in four of 14 patients who underwent biopsy (28.6%). Rectourethral fistula was observed in three cases (3.3%). Urinary retention was observed in six cases (6.6%). Incontinence (requiring pad use) was reported in five cases (5.5%). Intercourse was reported in 10 of 20 patients (50%) who reported potency before salvage focal cryoablation. CONCLUSIONS. The outcomes from this observational study indicate that salvage focal cryoablation can be an effective treatment with encouraging potency preservation for patients with locally recurrent PCa after radiotherapy. However, other morbidity including rectourethral fistula and incontinence are not clearly lower than for patients treated with salvage whole gland cryoablation. Studies with longer follow-up, more patients, and direct comparison to salvage whole gland cryoablation are needed before recommending salvage focal cryoablation as a standard treatment option for these patients. Prostate 75: 1–7, 2015. # 2014 Wiley Periodicals, Inc.
KEY WORDS:
cryoablation; focal therapy; prostate cancer; radiotherapy; salvage
Herbert Ruckle (Olympus). Julio Powsang (Watermark Research). J. Stephen Jones (Predictive Biosciences, Photocare, Healthtronics, Cook). Conflict of interest: Nothing to declare (Yong-Hong Li, Ahmed Elshafei, Gautum Agarwal)
Correspondence to: J. Stephen Jones, MD, Vice President Regional Medical Operations Cleveland Clinic Regional Hospitals & Family Health Centers Professor & Horvitz/Miller Distinguished Chair 9500 Euclid Avenue, Q10-1, OH 44195. E-mail: [email protected] Received 6 July 2014; Accepted 23 July 2014 DOI 10.1002/pros.22881 Published online 4 October 2014 in Wiley Online Library (wileyonlinelibrary.com).
ß 2014 Wiley Periodicals, Inc.
2
Li et al.
INTRODUCTION Approximately 25% patients with prostate cancer (PCa) undergo radiotherapy as a primary treatment option according to SEER (Surveillance, Epidemiology and End Results) data [1]. Biochemical failure after radiotherapy for localized PCa can occur in approximately 10–60% [2–4]. The most common salvage treatment for these patients is androgen-deprivation therapy [3]. However, this is not a curative treatment. Furthermore, it can have an impact on quality of life and increase the risk of cardiovascular mortality and skeletal fracture [5]. Many patients with biopsy-proven locally recurrent PCa may be suitable for local salvage therapy with curative intent. Local salvage treatment options include radical prostatectomy (RP), cryoablation, high-intensity focused ultrasonography, and brachytherapy. Since salvage RP is limited in clinical practice due to much higher morbidity than primary RP [6], salvage whole gland cryoablation has emerged as an option with acceptable long-term oncological outcomes and lower side effects. However, significant side effects are possible, including urinary retention (3.0–8.5%), incontinence (4.4–13.0%), rectourethral fistula (0–3.3%), and erectile dysfunction (61.5–100%) [7,8,9]. In order to decrease complications of salvage cryoablation, several investigators have tried to apply salvage focal cryoablation to small numbers of patients with biopsy-proven unilateral recurrent PCa after radiotherapy. Salvage focal cryoablation of the prostate for locally recurrent PCa after radiotherapy failure was first reported by Eisenberg and Shinohara in 2008 [10]. Several recent publications also showed encouraging outcomes of salvage focal cryoablation for locally recurrent PCa after radiotherapy failure. However, all these studies had small patients’ numbers (the biggest number is 44 patients) [9,11,12]. In this study, we report the outcomes of salvage focal cryoablation at a large number of academic and community centers that have participated in the COLD Registry. To our knowledge, this is the largest data set assembled for salvage focal cryoablation for the treatment of localized PCa recurrence after radiotherapy.
MATERIALS AND METHODS The COLD Registry was developed in an effort to provide a platform for academic and community urologists to gather cumulative data to advance the awareness and science of prostate cryoablation through evidence-based medical outcomes. Currently, The Prostate
over 7,000 patient records from 44 active sites are included in the registry. Although industry sponsored (HealthTronics; Austin, TX), all registry data collection, statistical analysis, and reporting was performed by an independent research company (Watermark Research Partners; Indianapolis, IN). The COLD Registry is supervised by a scientific board of urologists, and an independent audit of the scientific data is conducted yearly at randomly chosen centers in order to ensure the accuracy of data. All participating sites that were required to do so had approval from their institutional review board (IRB) before submission of any data to the registry database. A global IRB protocol has been in place since 2006 [13,14]. Patient data were entered into the COLD Registry classified as “primary” or “salvage” cryoablation and were further divided into “whole-gland” and “partial-gland” cryoablation. The use of neoadjuvant hormone ablation before cryoablation and adjuvant hormone ablation after cryoablation was noted. On November 5, 2013, we queried the COLD Registry to identify men who had undergone salvage partial gland prostate cryoablation for locally recurrent PCa after radiotherapy between 1999 and 2012. A total of 102 patients have undergone salvage focal cryotherapy within the COLD Registry. Eleven patients that received adjuvant hormone ablation were excluded from the study because of the likelihood that prostate specific antigen (PSA) values were misleadingly reduced by androgen deprivation. Ninety-one patients served as our study population. Any patient that had any length of androgen deprivation prior to treatment was defined as having neoadjuvant hormonal ablation, even if the purpose of this precryoablation treatment was unknown. Incontinence was defined as any pad use 12 months after salvage focal cryoablation. Potency was defined by the ability to have intercourse 12 months after salvage focal cryoablation. Post salvage focal cryoablation prostate biopsy was performed at physician discretion. Biochemical failure was defined using the Phoenix definition (nadir þ 2 ng/ml), which is the most commonly reported criterion, since no universally accepted definition of success has been identified in this setting [15]. Data were summarized using descriptive statistics. Continuous variables were compared with the Mann– Whitney U-test and categorical variables were compared with the Chi-squared test or Fisher’s exact test, as appropriate. The Kaplan–Meier method was used in the assessment of biochemical disease-free survival (bDFS) for the entire study population and for our subgroup analysis of bDFS stratified by neoadjuvant hormone ablation status. All statistics were two-sided,
Salvage Focal Prostate Cryoablation
3
and a P-value of
